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Postpartum depression (PPD) poses significant challenges, affecting both mothers and children, with substantial societal and economic implications. Internet-based cognitive behavioral therapy interventions (iCBT) offer promise in addressing PPD, but their economic impact remains unexplored. This study aimed to evaluate the cost-utility of Be a Mom, a self-guided iCBT intervention, compared with a waiting-list control among postpartum women at high risk of PPD. This economic evaluation was conducted alongside a 14-month randomized controlled trial adopting a societal perspective. Participants were randomized to Be a Mom (n = 542) or a waitlisted control group (n = 511). Self-report data on healthcare utilization, productivity losses, and quality-adjusted life years (QALYs) were collected at baseline, post-intervention, and 4 and 12 months post-intervention. Incremental cost-effectiveness ratios (ICERs) were calculated, and cost-effectiveness acceptability curves were generated using nonparametric bootstrapping. Sensitivity analyses were conducted to assess result robustness. Over 14 months, Be a Mom generated a QALY gain of 0.0184 (0.0022, 0.0346), and cost savings of EUR 34.06 (−176.16, 108.04) compared to the control group. At a willingness to pay of EUR 20,000, Be a Mom had a 97.6 % probability of cost-effectiveness. Results have limitations due to self-selected sample, potential recall bias in self-reporting, missing data, limited follow-up, and the use of a waiting-list control group. This study addresses a critical gap by providing evidence on the cost-utility of an iCBT intervention tailored for PPD prevention. Further research is essential to identify scalable and cost-effective interventions for reducing the burden of PPD. • First randomized trial on cost-utility of iCBT for prevention of PPD • Compared to the control group, the intervention yielded more QALYs and less costs over 14 months. • The intervention had a 97.6 % probability of cost-effectiveness at a WTP of EUR 20,000. • iCBT has the potential to be adopted as a cost-effective preventive strategy for PPD. [ABSTRACT FROM AUTHOR]

In an inpatient treatment center for pediatric obesity, the effectiveness of an emotion regulation (ER) training on top of the multidisciplinary obesity treatment (MOT) was tested by means of an RCT. The ER training was evaluated on primary outcomes: ER and emotional eating, and secondary outcomes: well-being and weight loss, taking into account pre, post, and follow-up measurements. Of the 115 10- to-14-year old adolescents with obesity (52.2% girls), 65 were allocated to the ER training. Physicians measured their height and weight objectively (4 times). Participants also filled out questionnaires on ER competencies (ER abilities and ER strategies), emotional eating and well-being (3 times). Significant pre-post interactions were found for "emotional awareness," "problem solving," and "evoking a positive mood." Moreover, the positive effects of the ER training on emotion regulation strategies were maintained at follow-up. Concerning well-being, no significant pre-post interaction effects were found but a significant interaction effect was found when comparing pre with follow-up. Analyses show a significant main effect of time on weight loss, but this was not qualified by a Time × Condition interaction effect. The current RCT study shows limited but promising effects of adding an ER training to the MOT. Further research should investigate whether the positive short-term effects will be maintained. [ABSTRACT FROM AUTHOR]

Preclinical studies support a protective role for aspirin in early diabetic retinopathy (DR), but the findings from randomized trials are limited. We present randomized evidence for the efficacy and safety of aspirin on DR outcomes. A substudy of the A Study of Cardiovascular Events in Diabetes (ASCEND) double-masked, randomized, placebo-controlled trial of 100 mg aspirin daily for the primary prevention of serious cardiovascular events in people with diabetes. Fifteen thousand four hundred eighty United Kingdom adults at least 40 years of age with diabetes. Linkage to electronic National Health Service Diabetic Eye Screening Programme records in England and Wales and confirmation of participant-reported eye events via medical record review were carried out. Log-rank methods were used for intention-to-treat analyses of time until the first primary efficacy and safety outcomes. The primary efficacy end point was the first record of referable disease after randomization, a composite of referable retinopathy or referable maculopathy based on the grading criteria defined by the United Kingdom National Screening Committee. The primary safety outcome was the first sight-threatening eye bleed, defined as clinically significant bleeding in the eye that resulted in unresolved visual loss or required an urgent intervention such as laser photocoagulation, vitreoretinal surgery, intraocular injection, or a combination thereof. Linkage data were obtained for 7360 participants (48% of those randomized in ASCEND). During the mean follow-up of 6.5 years, 539 participants (14.6%) experienced a referable disease event in the aspirin group, compared with 522 participants (14.2%) in the placebo group (rate ratio, 1.03; 95% confidence interval [CI], 0.91–1.16; P = 0.64). No statistically significant between-group difference was found in the proportions of sight-threatening eye bleed events (57 participants [0.7%] and 64 participants [0.8%], respectively; rate ratio, 0.89; 95% CI, 0.62–1.27). These data exclude any clinically meaningful benefits of aspirin for DR, but give reassurance regarding the ophthalmologic safety of aspirin. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

To determine whether primary trabeculectomy or medical treatment produces better outcomes in terms of quality of life (QoL), clinical effectiveness, and safety in patients with advanced glaucoma. Multicenter randomized controlled trial. Between June 3, 2014, and May 31, 2017, 453 adults with newly diagnosed advanced open-angle glaucoma in at least 1 eye (Hodapp classification) were recruited from 27 secondary care glaucoma departments in the United Kingdom. Two hundred twenty-seven were allocated to trabeculectomy, and 226 were allocated medical management. Participants were randomized on a 1:1 basis to have either mitomycin C-augmented trabeculectomy or escalating medical management with intraocular pressure (IOP)-reducing drops as the primary intervention and were followed up for 5 years. The primary outcome was vision-specific QoL measured with the 25-item Visual Function Questionnaire (VFQ-25) at 5 years. Secondary outcomes were general health status, glaucoma-related QoL, clinical effectiveness (IOP, visual field, and visual acuity), and safety. At 5 years, the mean ± standard deviation VFQ-25 scores in the trabeculectomy and medication arms were 83.3 ± 15.5 and 81.3 ± 17.5, respectively, and the mean difference was 1.01 (95% confidence interval [CI], –1.99 to 4.00; P = 0.51). The mean IOPs were 12.07 ± 5.18 mmHg and 14.76 ± 4.14 mmHg, respectively, and the mean difference was –2.56 (95% CI, –3.80 to –1.32; P < 0.001). Glaucoma severity measured with visual field mean deviation were –14.30 ± 7.14 dB and –16.74 ± 6.78 dB, respectively, with a mean difference of 1.87 (95% CI, 0.87–2.87 dB; P < 0.001). Safety events occurred in 115 (52.2%) of patients in the trabeculectomy arm and 124 (57.9%) of patients in the medication arm (relative risk, 0.92; 95% CI, 0.72–1.19; P = 0.54). Serious adverse events were rare. At 5 years, the Treatment of Advanced Glaucoma Study demonstrated that primary trabeculectomy surgery is more effective in lowering IOP and preventing disease progression than primary medical treatment in patients with advanced disease and has a similar safety profile. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

Pregnant women often experience anxiety due to pregnancy, negatively impacting their and their fetus' health. Non-pharmacological interventions, such as virtual reality (VR), could reduce anxiety levels, potentially impacting non-stress tests or the physiological responses of the pregnant woman and the fetus. A randomized clinical trial conducted between February and December 2022 involved 286 term pregnant women. They were divided into a VR intervention group (146 women) and a control group (140 women). The intervention consisted of 20 min of 3D glasses with images and sounds during a third-trimester nonstress test. Anxiety was measured using the Spielberg State-Trait Anxiety Inventory (STAI), alongside physiological parameters. The VR group exhibited lower anxiety levels compared to controls (STAI score: Rosenthal's r: −0.54, p = 0.01; state anxiety: Rosenthal's r: −0.40, p = 0.001; trait anxiety: Rosenthal's r: −0.41, p = 0.001). Within the VR group, there was a significant reduction in trait anxiety (Rosenthal's r, 1.27; p < 0.001) and total anxiety (Rosenthal's r, 1.63; p < 0.001) post-intervention, along with decreased systolic blood pressure (p < 0.001), diastolic blood pressure (p < 0.001), and maternal heart rate (p = 0.02). Future research could explore additional pregnancy-related variables, such as postpartum anxiety. The results confirm that the use of VR is beneficial for pregnant women and their fetuses, as it decreases anxiety levels, and improves physiological parameters such as blood pressure and maternal heart rate during the nonstress test. VR is a technique that is easy to integrate into the healthcare system due to its non-invasive and non-pharmacological nature. • Virtual reality has proven to be an effective technique in reducing anxiety of pregnant women during NST. • Anxiety is related to higher blood pressure and heart rate values in pregnant women during NST. • Blood pressure and heart rate in pregnant women improved when virtual reality was used as a therapy. [ABSTRACT FROM AUTHOR]

Depressed patients who have become victim of violence are prone to revictimization. However, no evidence-based interventions aimed at reducing revictimization in this group exist. This multicenter randomized controlled trial evaluated the effectiveness of an internet-based emotion regulation training (iERT) added to TAU in reducing revictimization, emotion dysregulation, and depressive symptoms in recently victimized, depressed patients compared to TAU alone. Adult outpatients (N = 153) with a depressive disorder who had experienced threat, physical assault, or sexual assault within the previous three years were randomly allocated to TAU+iERT (n = 74) or TAU (n = 79). TAU involved psychotherapy (mainly cognitive behavioral therapy [77.8 %]). iERT comprised six guided online sessions focused on the acquisition of adaptive emotion regulation skills. The primary outcome measure was the number of revictimization incidents at 12 months after baseline, measured with the Safety Monitor. Analyses were performed according to the intention-to-treat principle. Both groups showed a large decrease in victimization incidents. Mixed-model negative binomial regression analyses showed that TAU+iERT was not effective in reducing revictimization compared to TAU (IRR = 0.97; 95%CI = 0.64,1.46; p =.886). Linear mixed-model analyses demonstrated that TAU+iERT yielded a larger reduction of emotion dysregulation (B = −7.217; p =.046; Cohens d = 0.33), but not depressive symptoms (B = −1.041; p =.607) than TAU. The study was underpowered to detect small treatment effects. Additionally, uptake of iERT was quite low. Although TAU+iERT resulted in a larger decrease of emotion dysregulation than TAU alone, it was not effective in reducing revictimization and depressive symptoms. Patients' revictimization risk substantially decreased during psychotherapy. • Online emotion regulation training improved emotion regulation in depressed patients. • iERT did not reduce revictimization rates or depressive symptoms compared to TAU. • Violent victimization rates decreased substantially during psychotherapy. [ABSTRACT FROM AUTHOR]

Ivermectin is an antiparasitic drug administered to hundreds of millions of people worldwide. Fundamental research suggests that ivermectin is effective against coronavirus disease 2019 (COVID-19); therefore, we investigated the efficacy and safety of ivermectin as a COVID-19 treatment option. This multi-regional (Japan and Thailand), multicenter, placebo-controlled, randomized, double-blind, parallel-group, Phase III study evaluated the efficacy and safety of ivermectin in patients with mild COVID-19 (IVERMILCO Study). The participants took a specified number of the investigational product (ivermectin or placebo) tablets of, adjusted to a dose of 0.3–0.4 mg/kg, orally on an empty stomach once daily for three days. The primary efficacy endpoint was the time at which clinical symptoms first showed an improving trend by 168 h after investigational product administration. A total of 1030 eligible participants were assigned to receive the investigational product; 502 participants received ivermectin and 527 participants received a placebo. The primary efficacy endpoint was approximately 96 h (approximately four days) for both ivermectin and placebo groups, which did not show statistically significant difference (stratified log-rank test, p = 0.61). The incidence of adverse events and adverse drug reactions did not show statistically significant differences between the ivermectin and placebo groups (chi-square test, p = 0.97, p = 0.59). The results show that ivermectin (0.3–0.4 mg/kg), as a treatment for patients with mild COVID-19, is ineffective; however, its safety has been confirmed for participants, including minor participants of 12 years or older (IVERMILCO Study ClinicalTrials.gov number, NCT05056883.). [ABSTRACT FROM AUTHOR]

Our aim is to investigate the effects of the submucoperichondrial application of Platelet Rich Plasma (PRP) on nasal mucosal healing after septoplasty surgery. This prospective randomized observational study was conducted between July 2019 and February 2021, with 40 patients aged 18–60 years who underwent closed the only septoplasty operation for similar septal deviations. Patient divided into two group; 21 patients were placed in PRP group to which PRP was applied on all mucosal surface and submucoperichondrial area of septum and 19 patients were placed in control group to which saline solution was applied on same regions. Nasal obstruction score, mucociliary clearance time, presence of nasal crusting, and bleeding time were evaluated on 5th, 10th, 15th day after surgery and compared between groups. Intranasal crusting on day 10 was found to be lower in the PRP group (n :13 68.4 %) than control group (n :7 33.3 %) with a statistically significant difference (p = 0.028). The nasal obstruction score on day 10 and 15 were found to be lower in the PRP group (3,33 ± 2,75, 2,07 ± 2,20) (than the control group (5,44 ± 2,26, 3,37 ± 1,92) with a statistically significant difference (p = 0,003, p = 0,009). The mucociliary clearance rate was found to be higher and the bleeding time was found to be lower in the PRP group, but a statistically significant difference was not observed. Application of submucoperichondrial PRP could have beneficial effects on nasal mucosal repair, nasal crusting, and congestion after septoplasty surgery. [ABSTRACT FROM AUTHOR]

[Display omitted] • First trial using tDCS for Parkinsońs disease-related pain has been performed. • tDCS alleviates perceived pain and increases descending inhibitory systems in Parkinsońs disease patients. • Conditioned Pain Modulation could mediate pain relief in Parkinsońs disease. To evaluate the effects of transcranial direct current stimulation (tDCS) on Parkinson's disease (PD)-related pain. This triple-blind randomized controlled trial included twenty-two patients (age range 38–85, 10 male) with PD-related pain. Eleven subjects received ten sessions of 20 minutes tDCS over the primary motor cortex contralateral to pain at 2 mA intensity. Eleven subjects received sham stimulation. Outcome measures included changes in the Kinǵs Parkinsońs Pain Scale (KPPS), Brief Pain Inventory (BPI), widespread mechanical hyperalgesia (WMH), temporal summation of pain (TS), and conditioned pain modulation (CPM). Significant differences were found in KPPS between groups favoring the active-tDCS group compared to the sham-tDCS group at 15-days follow-up (p = 0.014) but not at 2 days post-intervention (p = 0.059). The active-group showed significant improvements over the sham-group after 15 days (p = 0.017). Significant changes were found in CPM between groups in favor of active-tDCS group at 2 days post-intervention (p = 0.002) and at 15 days (p = 0.017). No meaningful differences were observed in BPI or TS. tDCS of the primary motor cortex alleviates perceived PD-related pain, reduces pain sensitization, and enhances descending pain inhibition. This is the first study to test and demonstrate the use of tDCS for improving PD-related pain. [ABSTRACT FROM AUTHOR]

Preclinical studies support a protective role for omega-3 fatty acids (FAs) on diabetic retinopathy (DR), but these observations have not been confirmed in randomized trials. We present randomized evidence for the effects of omega-3 FAs on DR outcomes. A substudy of the A Study of Cardiovascular Events iN Diabetes (ASCEND) double-blind, randomized, placebo-controlled trial of 1 g omega-3 fatty acids (containing 460 mg eicosapentaenoic acid and 380 mg docosahexaenoic acid) daily for the primary prevention of serious cardiovascular events, in 15 480 UK adults at least 40 years of age, with diabetes. Fifteen thousand four hundred eighty adults at least 40 years of age from the United Kingdom with diabetes from the ASCEND cohort. Linkage to electronic National Health Service Diabetic Eye Screening Programme records in England and Wales and confirmation of participant-reported eye events via medical record review. Log-rank and stratified log-rank methods were used for intention-to-treat analyses of time until the main outcomes of interest. The primary efficacy endpoint was time to the first postrandomization recording of referable disease, a composite of referable retinopathy (R 2 or R 3a/s) or referable maculopathy (M 1) based on the grading criteria defined by the United Kingdom National Screening Committee. Secondary and tertiary outcomes included the referable disease outcome stratified by the severity of DR at baseline, any progression in retinopathy grade, and incident diabetic maculopathy. Linkage data were obtained for 7360 participants (48% of those who were randomized in ASCEND). During their mean follow-up of 6.5 years, 548 participants (14.8%) had a referable disease event in the omega-3 FAs group, compared with 513 participants (13.9%) in the placebo group (rate ratio, 1.07; 95% confidence interval, 0.95–1.20; P = 0.29). There were no statistically significant between-group differences in the proportion of events for either of the secondary or tertiary outcomes. Representing the largest prospective test of its kind to date, these data exclude any clinically meaningful benefits of 1 g daily omega-3 FAs on DR. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

The pathophysiology and the potential risks of placental transfusion (PT) differ substantially in preterm infants, necessitating specific studies in this population. This study aimed to evaluate the safety and efficacy of PT in preterm infants from the perspective of long-term neurodevelopmental outcomes. We conducted a systematic literature search using placental transfusion, preterm infant, and its synonyms as search terms. Cochrane Central Register of Controlled Trials, Medline, and Embase were searched until March 07, 2023. Two reviewers independently identified, extracted relevant randomized controlled trials, and appraised the risk of bias. The extracted studies were included in the meta-analysis of long-term neurodevelopmental clinical outcomes using fixed-effects models. A total of 5612 articles were identified, and seven randomized controlled trials involving 2551 infants were included in our meta-analysis. Compared with immediate cord clamping (ICC), PT may not impact adverse neurodevelopment events. No clear evidence was found of a difference in the risk of neurodevelopmental impairment (risk ratio [RR]: 0.89, 95% confidence interval [CI]: 0.76 to 1.03, P = 0.13, I2 = 0). PT was not associated with the incidence of cerebral palsy (RR: 1.23, 95% CI: 0.59 to 2.57, P = 0.79, I2 = 0). Analyses showed no differences between the two interventions in cognitive, language, and motor domains of neurodevelopment. From the perspective of long-term neurodevelopment, PT at preterm birth may be as safe as ICC. Future studies should focus on standardized, high-quality clinical trials and individual participant data to optimize cord management strategies for preterm infants after birth. [ABSTRACT FROM AUTHOR]

Social disconnection is common and causes significant impairment in anxiety and depressive disorders, and it does not respond sufficiently to available treatments. The positive valence system supports social bond formation and maintenance but is often hyporesponsive in people with anxiety or depression. We conducted an experimental therapeutics trial to test the hypothesis that targeting positive valence processes through cognitive and behavioral strategies would enhance responsivity to social rewards, a core mechanism underlying social connectedness. Sixty-eight adults who endorsed clinically elevated anxiety and/or depression with social impairment were randomized 1:1:1 to 5 (n = 23) or 10 (n = 22) sessions of amplification of positivity (AMP) treatment or waitlist (n = 23). Pre- to posttreatment change in striatal activity (primary outcome) during social reward anticipation was measured using functional magnetic resonance imaging, and reactivity to a social affiliation task (secondary) and self-reported social connectedness (exploratory) were examined. Primary analyses compared AMP (doses combined) versus waitlist. A second aim was to compare the effects of different doses. AMP engaged the hypothesized treatment target, leading to greater striatal activation during anticipation of social rewards versus waitlist (d = 1.01 [95% CI = 0.42–1.61]; largest striatal volume). AMP yielded larger improvements in positive affect and approach behavior during the affiliation task (but not other outcomes) and social connectedness. Larger striatal and social connectedness increases were observed for 5-session versus 10-session AMP (d range = 0.08–1.03). Teaching people with anxiety or depression strategies to increase positive thoughts, behaviors, and emotions enhances activity in brain regions that govern social reward processing and promotes social connectedness. Social reward sensitivity may be a transdiagnostic target for remediating social disconnection. [ABSTRACT FROM AUTHOR]

Subjective support could ameliorate the adverse effect of (pre)frailty on depressive symptoms. However, there is scarce evidence regarding subjective support-focused intervention in preventing depression among (pre)frail community-dwelling older adults. This study aims to explore the effectiveness of subjective support-focused cognitive behavioral therapy (SS-CBT) in preventing depression among this group of population. A total of 100 community-dwelling (pre)frail older adults were recruited from six communities in a Chinese city and were randomized to an 8-week SS-CBT group or a wait-list control group. Depressive symptoms and subjective support were assessed at baseline (T0), and at 8 week (T1), 12 week (T2), 16 week (T3) after randomization. Generalized estimating equation was used to examine the effectiveness of SS-CBT on depressive symptoms and subjective support. Hierarchical linear regression models and Bootstrapping method were used to examine whether subjective support mediated the effectiveness of SS-CBT on depressive symptoms. Participants in SS-CBT group reported significant reduction in depressive symptoms (Wald χ 2 = 20.800, p < 0.001) and improvement in subjective support (Wald χ 2 = 92.855, p < 0.001) compared to those in wait-list control group. Changes in subjective support mediated the effectiveness of SS-CBT on changes in depressive symptoms. Restricted regions to recruit participants, inclusion of the most motivated participants, lack of diagnosis of depression, potential experimenter bias and contamination, short follow-up period, and lack of an active control group. The findings support the benefits of SS-CBT in preventing depression among (pre)frail community-dwelling older adults, and provide insight into possible mechanisms. • (Pre)frail older adults are more likely to experience depression. • Subjective support is effective in protecting depression. • Cognitive behavioral therapy has the potential to improve subjective support. [ABSTRACT FROM AUTHOR]

• ECT is effective but has cognitive side-effects; add-on treatments are needed. • No change was seen in complex cognitive processing with ECT or EPO. • EPO infusions during ECT led to faster autobiographical memory recall. • EPO reduced memory-related parietal cortex activity compared to saline. • Autobiographical memory may be a sensitive measure for ECT side-effects. Electroconvulsive therapy (ECT) is one of the most effective and rapid-acting treatment for severe depression but is associated with cognitive side-effects. Identification of add-on treatments that counteract these side-effects would be very helpful. This randomized, double-blinded, placebo-controlled, parallel-group study investigated the effects of four add-on erythropoietin (EPO; 40,000 IU/ml) or saline (placebo) infusions over 2.5 weeks of ECT (eight ECT sessions) in severely depressed patients with unipolar or bipolar depression. Neuropsychological assessments were conducted pre-ECT, three days after the eighth ECT (week 4), and at a 3-month follow-up. Further, functional magnetic resonance imaging (fMRI) was conducted after the eighth ECT. The primary outcome was change from pre- to post-ECT in a 'speed of complex cognitive processing' composite. Secondary outcomes were verbal and autobiographical memory. Of sixty randomized patients, one dropped out before baseline. Data were thus analysed for 59 patients (EPO, n = 33; saline, n = 26), of whom 28 had fMRI data. No ECT-related decline occurred in the primary global cognition measure (p s≥0.1), and no effect of EPO versus saline was observed on this outcome (p s≥0.3). However post-ECT, EPO-treated patients exhibited faster autobiographical memory recall than saline-treated patients (p = 0.02), which was accompanied by lower memory-related parietal cortex activity. The absence of global cognition changes with ECT and EPO, coupled with the specific impact of EPO on autobiographical memory recall speed and memory-related parietal cortex activity, suggests that assessing autobiographical memory may provide increased sensitivity in evaluating and potentially preventing cognitive side-effects of ECT. ClinicalTrials.gov: NCT03339596, EudraCT no.: 2016-002326-36. [ABSTRACT FROM AUTHOR]

Discrepancies between sleep diaries and actigraphy occur among individuals with insomnia. Cognitive behavioural therapy for insomnia (CBT-I) improves insomnia but the impact on discrepancy is unclear. This study examined CBT-I's effects on actigraphy-diary discrepancy and explored sleep-related beliefs and attitudes as a mediator. Participants were 108 (age M ± SD = 47.23 ± 12.42, 67.60 % female) adults with insomnia and major depressive disorder from the Treatment of Insomnia and Depression study. They were randomized to 7 sessions of CBT-I or sham Quasi-Desensitization Therapy for Insomnia (DTI), plus 16 weeks of antidepressants. Two weeks of actigraphy and sleep diary were collected at baseline, mid-treatment, end-treatment. Differences between sleep diary and actigraphy total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), and sleep efficiency (SE) were calculated. Participants completed Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS) at baseline and mid-treatment. At baseline, diary (versus actigraphy) TST was shorter (1.1 ± 1.41h), whilst SOL (21.64 ± 41.25min) and WASO (17.45 ± 61.99min) were longer. Mixed effects models using daily data showed that after adjusting for age and sex, participants in the CBT-I group (versus DTI) showed greater reduction in all actigraphy-diary discrepancy domains (all p-values <.01), reductions evident from mid-treatment. Group differences on actigraphy-diary discrepancy reductions in TST, SOL, and SE (not WASO) were mediated by changes in DBAS from baseline to mid-treatment (all p-values <.05). Changes in discrepancy did not mediate insomnia symptom changes (p-values >.39). CBT-I reduced actigraphy-diary discrepancy in individuals with comorbid insomnia and depression; this reduction was associated with improved sleep-related attitudes, a therapeutic target of CBT-I. TRIAD (Treatment of Insomnia and Depression): Improving Depression Outcome by Adding Insomnia Therapy to Antidepressants. Prospectively registered with Clinical Trials (NCT00767624). MH078924, MH078961, MH079256. • Individuals with insomnia and depression reported shorter and worse sleep compared to actigraphy measures. • CBT-I reduced actigraphy-diary discrepancy in these individuals. • Discrepancy reduction was associated with improved sleep-related attitudes and beliefs. [ABSTRACT FROM AUTHOR]

We evaluated if Insulin-like Factor 3, basal and human chorionic gonadotropin (hCG)-stimulated testosterone could predict beneficial effects of testosterone replacement among 69 testicular cancer survivors with mild Leydig cell insufficiency randomly assigned to testosterone replacement therapy or placebo. Although the patients with Insulin-like Factor 3 and hCG-stimulated testosterone below median at baseline had less fat mass after 12 months of testosterone replacement therapy compared with placebo, we cannot recommend testosterone replacement therapy in specific subgroups of men with mild Leydig cell insufficiency. Introduction: Mild Leydig cell insufficiency affects a substantial proportion of testicular cancer survivors. Previous studies have not shown a beneficial effect of testosterone replacement therapy, however, with a pronounced interindividual effect. Thus, biomarkers identifying the subgroups that might benefit are wanted. We aimed to determine if insulinlike factor 3 (INSL3), basal and human chorionic gonadotropin (hCG)-stimulated testosterone can predict the effect of testosterone replacement therapy in testicular cancer survivors with mild Leydig cell insufficiency. Patients and Methods: We randomized adult testicular cancer survivors with mild Leydig cell insufficiency 1:1 to 12 months of transdermal testosterone replacement therapy (Tostran gel 2%) or placebo. INSL3, basal, and hCG-stimulated testosterone were measured at baseline. Outcomes (glucose, insulin, HbA1C, lipids, blood pressure, and body composition) were measured at baseline, 6 and 12 months. We applied a linear mixed-effect model comparing patients receiving testosterone with placebo in subgroups by biomarker. Results: We included and randomized 69 patients between October 2016 and February 2018. Patients with INSL3 and hCG-stimulated testosterone concentrations below the median had a -1.7 kg (95% CI: -3.1, -0.4) and -2.0 kg (95% CI: -3.5, -0.6) change in fat mass after 12 months of testosterone replacement therapy compared with placebo. This was not the case in patients with INSL3 and hCG-stimulated testosterone above the median. We did not find any effect of these biomarkers on glucose, insulin, HbA1c, or lipids. Conclusion: Patients with INSL3 and hCG-stimulated testosterone concentrations below the median had decreased fat mass after 1 12 months of testosterone replacement therapy compared with placebo. It should be evaluated in larger trials if these biomarkers can be used as predictive markers identifying testicular cancer patients with mild Leydig cell insufficiency who might benefit from testosterone substitution. [ABSTRACT FROM AUTHOR]

Insomnia is a significant health issue associated with various systemic diseases. Transcranial alternating current stimulation (tACS) has been proposed as a potential intervention for insomnia. However, the efficacy and mechanisms of tACS in chronic insomnia remain unclear. Accordingly, this study aimed to investigate the efficacy of tACS in treating chronic insomnia in adults and assess the impact of age on its effectiveness using a large sample from two centers. A total of 120 participants with chronic insomnia underwent 20 daily sessions of tACS (duration: 40 min, frequency: 77.5 Hz, and intensity: 15 mA) or sham tACS targeting the forehead and both mastoid areas over 4 weeks. Assessments were conducted at baseline, post-treatment, and 4-week follow-up. Primary outcomes included sleep quality and efficiency, onset latency, total sleep time, and daily disturbances. Secondary outcomes included depression, anxiety, and clinical impression. Compared with the control group, the tACS group demonstrated improved sleep quality and efficiency, increased total sleep time, and reduced daily disturbance (all ps < 0.01). Moreover, tACS had a significant effect on clinical impression (p < 0.001), but not depression and anxiety scores. Subgroup analyses revealed that older participants experienced significant benefits from tACS in sleep quality, efficiency, and overall insomnia reduction at post-treatment and follow-up (p < 0.001). Notably, improved insomnia correlated with attenuated depressive and anxiety symptoms. These findings suggest that tACS may be an effective intervention for chronic insomnia within an eight-week timeframe, and age affects the response to tACS in terms of insomnia improvement. • tACS improved sleep quality and efficiency. • tACS had a significant effect on clinical impression. • Older participants experienced significant benefits from tACS. • Improved insomnia correlated with attenuated depressive symptoms, anxiety symptoms and clinical impression. • tACS may be an effective intervention for chronic insomnia. [ABSTRACT FROM AUTHOR]

This paper summarizes the results of the Improving Mood with Psychoanalytic and Cognitive Therapies (IMPACT) study and its implications for psychological treatment of adolescents with moderate to severe unipolar major depression. IMPACT was a pragmatic, superiority, randomized controlled trial conducted in the United Kingdom, which compared the clinical and cost-effectiveness of short-term psychoanalytic therapy (STPP), cognitive−behavioral therapy (CBT), and a brief psychosocial intervention (BPI) in reducing depression symptoms in 465 adolescents with unipolar major depression, aged 11 to 17 years. Although this was a clinically heterogeneous group of adolescents, some symptoms (eg, sleep and concentration difficulties, irritability/anger) were common and disabling. The trial reported no significant difference among the 3 treatments in reducing depression symptoms. One year after treatment, 84% of participants showed improvement in depressive symptoms (<50% of baseline symptoms) and improved psychosocial functioning, achieving this through different symptom reduction trajectories. Although participants attended fewer treatment sessions than planned, the 3 treatments were delivered with fidelity to their respective models. Ending treatment without therapist agreement occurred in 37% of cases. This was not associated with outcomes by treatment group. Adolescents emphasized the importance of the therapeutic relationship in all 3 treatments. Results suggest that although most adolescents respond to time-limited, structured psychological therapy, subgroups of depressed adolescents are likely to need additional treatment or support. These include adolescents who live in complex circumstances and/or who believe that their needs are not met in therapy, some who stop treatment early, and the 16% to 18% of adolescents who do not respond to treatment. Improving Mood and Preventing Relapse With Psychoanalytic Psychotherapy and Cognitive Behaviour Therapy; https://www.isrctn.com ; ISRCTN83033550. [ABSTRACT FROM AUTHOR]

As the prevalence of tramadol toxicity is increasing, managing these patients with the aim of treatment and complete recovery has become a major challenge for health care professionals. This study evaluated the short-term effects of IV lipid emulsion (ILE) administration in cases of tramadol poisoning. In this double-blind, randomized controlled trial, 120 patients with pure tramadol poisoning and a Glasgow Coma (GCS) score ≤ 12 referred to a poisoning center in Tehran, Iran were selected and randomly assigned 1:1 to receive ILE 20% (intervention) or 0.9% saline (control) after admission and primary stabilization. The patient's vital signs, GCS score, hospitalization duration, and rate of seizure occurrence were recorded and compared between the two groups. Mean (SD) age of participants was 25.3 (5.4) years and 84 (70%) were male. Mean (SD) ingested dose of tramadol was 3118 (244) mg, which was not different between the groups. Compared with controls, the ILE group had a higher level of consciousness after treatment (median [interquartile range] GCS score 12 [10–13] vs. 10 [8–12]; p = 0.03). In addition, length of hospitalization (median [interquartile range] (2 [1–3] days vs. 4 [4–6] days; p < 0.01) and rate of seizure occurrence were lower in the intervention group (16/60 vs. 30/60; p < 0.01). In the setting of tramadol poisoning with a decreased level of consciousness and based on our study's findings, administration of ILE is suggested to help manage patients in hospital emergency departments. However, larger trials might be needed to confirm these findings before entering the guidelines. [ABSTRACT FROM AUTHOR]

Peripheral venous cannulation is one of the most common procedures in medicine. A larger cannula allows higher rates of fluid to be provided if needed in a deteriorating patient; however, it is also perceived that larger-gauge cannula placement is associated with increased pain and procedural difficulty. This study aimed to compare the pain and procedural difficulty experienced during insertion between 18-gauge (18G) and 20-gauge (20G) cannulas. We conducted a single-blinded, randomized controlled trial on adult patients who required peripheral IV cannulation within a tertiary hospital emergency department between April and October 2018. Patients were randomized to either the 18G or 20G cannula group. The primary outcomes of the study—pain experienced by patients and procedural difficulties experienced by clinical staff—were recorded on two separate 10-cm visual analog scales. Other outcomes include first-attempt success rate, operator designation, complications, and the intent and actual use of the IV cannula were documented on preformatted questionnaires. Data from 178 patients were included in the analysis. Eighty-nine patients were allocated to each cannula group. There were no statistically or clinically significant differences between mean pain score (0.23; 95% CI 0.56–1.02; p = 0.5662) and mean procedural difficulty score (0.12; 95% CI 0.66–0.93; p = 0.7396). between the two groups. There was no difference in first-attempt success rate (73 of 89 vs. 75 of 89; p = 0.1288), complications (2 of 89 vs. 1 of 89) between the 20G group and 18G group, respectively. There was no significant difference between the 18G or 20G cannula for either pain experienced by patients or procedural difficulty experienced by clinicians. [ABSTRACT FROM AUTHOR]

Endothelin receptor antagonist (ERA) and phosphodiesterase 5 inhibitor (PDE5i) combination therapy is recommended for low-/intermediate-risk pulmonary arterial hypertension (PAH) patients. A fixed-dose combination of the ERA macitentan and PDE5i tadalafil (M/T FDC) in a once-daily, single tablet would simplify treatment. The multicenter, double-blind, adaptive phase 3 A DUE study investigated the efficacy and safety of M/T FDC vs macitentan 10 mg and vs tadalafil 40 mg monotherapies in PAH patients, including treatment-naïve and prior ERA or PDE5i monotherapy-treated patients. World Health Organization functional class II-III patients were randomized to M/T FDC, macitentan, or tadalafil depending on their PAH treatment (treatment-naïve, ERA, or PDE5i monotherapy) at baseline. The primary endpoint was change in pulmonary vascular resistance (PVR) at week 16. In total, 187 patients were randomized to single-tablet M/T FDC (n = 108), macitentan (n = 35), or tadalafil (n = 44). PVR reduction with M/T FDC was significantly greater vs macitentan (29%; geometric mean ratio 0.71; 95% CL: 0.61-0.82; P < 0.0001) and vs tadalafil (28%; geometric mean ratio 0.72; 95% CL: 0.64-0.80; P < 0.0001). Three patients died in the M/T FDC arm (judged unrelated to treatment). Adverse events (AEs) leading to discontinuation, serious AEs, and those of special interest (anemia, hypotension, and edema) were more frequent with M/T FDC. Macitentan and tadalafil FDC significantly improved PVR vs monotherapies in PAH patients, with a safety and tolerability profile consistent with the individual components. The A DUE study supports M/T FDC as a once-daily, single-tablet combination for initial therapy and escalation to double combination therapy in patients with PAH. (Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension [PAH]) [A DUE]; NCT03904693) [Display omitted] [ABSTRACT FROM AUTHOR]

For most patients, direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists for stroke prevention in atrial fibrillation and for venous thromboembolism treatment. However, randomized controlled trials suggest that DOACs may not be as efficacious or as safe as the current standard of care in conditions such as mechanical heart valves, thrombotic antiphospholipid syndrome, and atrial fibrillation associated with rheumatic heart disease. DOACs do not provide a net benefit in conditions such as embolic stroke of undetermined source. Their efficacy is uncertain for conditions such as left ventricular thrombus, catheter-associated deep vein thrombosis, cerebral venous sinus thrombosis, and for patients with atrial fibrillation or venous thrombosis who have end-stage renal disease. This paper provides an evidence-based review of randomized controlled trials on DOACs, detailing when they have demonstrated efficacy and safety, when DOACs should not be the standard of care, where their safety and efficacy are uncertain, and areas requiring further research. [Display omitted] • Target-specific (or direct) oral anticoagulants are preferred for prevention or treatment of thromboembolism in most patients with atrial fibrillation or venous thromboembolism. • DOACs should not be the standard treatment for patients with mechanical heart valves, atrial fibrillation with rheumatic mitral stenosis, or antiphospholipid syndrome. • The efficacy and safety of DOACs remain uncertain for several other clinical conditions and subgroups, and future studies should address those situations. [ABSTRACT FROM AUTHOR]

Up to 79 % of older adults with depression do not receive treatments commensurate with guideline recommendations. Metacognitive Training-Silver (MCT-Silver) is a low-intensity group training, which aims to reduce depressive symptoms by targeting (meta)cognitive beliefs. A randomized controlled trial comparing MCT-Silver (n = 41) to cognitive remediation (n = 39) was conducted with older adults with major depressive disorder and/or dysthymia. Clinician-rated depression (Hamilton Depression Rating Scale [HDRS, primary outcome]), self-reported depression (Beck Depression Inventory-II [BDI-II]), negative cognitive beliefs, positive metacognitive beliefs, rumination, health status, quality of life, and neurocognitive functioning were assessed at baseline, eight weeks (post) and three months (follow-up). Both groups demonstrated moderate to large reductions in depression. No superior effects of MCT-Silver on clinician-rated depression (HDRS) were detected. MCT-Silver led to greater reductions in self-reported depression and rumination at post- and follow-up. Despite this, scores at post- and follow-up assessments were similar for both groups. MCT-Silver's effect on depressive symptoms was moderated by baseline rumination, positive metacognitive beliefs and previous treatment experience. MCT-Silver was evaluated as superior according to patient appraisals. Conclusions are limited by divergent findings on measures of depression and that the study was conducted during the COVID-19 pandemic. Whereas no superior effect of MCT-Silver was found for the primary outcome, there was a significant effect of MCT-Silver for self-reported depression and rumination. Patients endorsing rumination and positive metacognitive beliefs as well as those without previous psychological treatment may benefit more from MCT-Silver. • We evaluated the efficacy of metacognitive training for depression in later life (MCT-Silver). • 80 patients were randomized to MCT-Silver or a cognitive remediation (CR) group. • MCT-Silver demonstrated statistically significant effects beyond CR on self-reported depression and rumination. • Despite statistically significant effects, total scores at post- and follow-up were similar between groups. [ABSTRACT FROM AUTHOR]

• We developed meaning-centered psychotherapy for eating disorders (MCP-ED). • The efficacy of MCP-ED was tested in women with high weight and shape concerns. • After MCP-ED and at follow-up, participants reported higher levels of life meaning. • MCP-ED also resulted in lower levels of eating disorder symptoms. • Future studies should test the effectiveness of MCP-ED in a clinical sample. Low meaning in life has been proposed as an important factor in the maintenance of eating disorders and previous findings suggest that targeting meaning might optimize treatment effectiveness. The current randomized controlled trial aimed to investigate the efficacy of meaning-centered psychotherapy adjusted for eating disorders (MCP-ED) to improve meaning in women with high weight and shape concerns. Female students with high weight and shape concerns (N = 134) were randomly assigned to the waiting-list control condition or the experimental condition, in which they followed six weekly individual sessions of MCP-ED. Self-report measures of meaning, eating disorder symptoms, general distress, psychological well-being, and satisfaction with meaningful life domains were completed at baseline, after the final session of MCP-ED or a 7-week waiting period, and at 4-week follow-up. Participants in the experimental condition showed a stronger increase in meaning than participants in the waiting-list condition after the intervention and at follow-up. The intervention also resulted in lower eating disorder symptoms and general distress, and higher psychological well-being and satisfaction with meaningful life domains. Findings support the efficacy of MCP-ED as an intervention to increase meaning and point to the relevance of examining whether adding MCP-ED to regular treatment might increase treatment effectiveness in individuals with eating disorders. [ABSTRACT FROM AUTHOR]

Current management guidelines for the treatment of carotid stenosis are controversial. We performed this meta-analysis to evaluate the perioperative safety of carotid artery stenting (CAS) and endarterectomy. We systematically searched EMBASE, PubMed, Web of Science, and the Cochrane Library from inception to November 10, 2022, for randomized controlled trials that compared CAS with carotid endarterectomy (CEA) among patients with carotid stenosis. The analyzed outcomes mainly included stroke, death, myocardial infarction (MI), cranial nerve palsy, the cumulative incidence of mortality, stroke, or MI and the cumulative incidence of death or stroke in the perioperative periods. The risk ratio (RR) and 95% confidence interval (95% CI) were calculated and pooled. Subgroup analyses were based on whether patients were symptomatic or asymptomatic. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. Seventeen randomized controlled trials with 12,277 participants (6514 and 5763 in the CAS and CEA groups, respectively) were included. Pooled analysis demonstrated that compared with CEA, CAS was associated with decreased risks of perioperative MI (RR = 0.47, 95% CI = 0.29∼0.77) and perioperative cranial nerve palsy (RR = 0.02, 95% CI = 0.01∼0.06) but higher risks of perioperative stroke (RR = 1.48, 95% CI = 1.18∼1.87) and cumulative incidence of death or stroke (RR = 1.52, 95% CI = 1.20∼1.93). The perioperative safety was equivalent between CAS and CEA. However, CEA may be preferred when considering both procedural safety and long-term efficacy in preventing recurrent stroke. [ABSTRACT FROM AUTHOR]

To determine whether early switch to oral antibiotic treatment in adults with neutropenic sepsis at low risk of complications is non-inferior to switching later. This non-inferiority, parallel-group, randomized, open-label clinical trial enrolled UK adults hospitalized with neutropenic sepsis. Participants were randomly assigned to either switch to oral ciprofloxacin plus co-amoxiclav within 12–24 hours or to continue intravenous treatment for at least 48 hours. The primary outcome was a composite measure of treatment failure, 14 days after randomization. The non-inferiority margin was 15%. There were 129 participants from 16 centres and 125 were assessed for the primary outcome. Of these, 113 patients completed protocolized treatment and comprised the per-protocol population. In total, 9 (14.1%) of 64 patients in the standard care arm met the primary end point, compared with 15 (24.6%) of 61 in the early switch arm, giving a risk difference of 10.5% (1-sided 95% CI, −∞% to 22%; p 0.14). In the per-protocol population, 8 (13.3%) of the 60 patients in the standard care arm met the primary end point, compared with 9 (17%) of 53 in the intervention arm giving a risk difference of 3.7% (one-sided 95% CI, −∞% to 14.8%; p 0.59). Duration of hospital stay was shorter in the intervention arm (median 2 [inter-quartile range (IQR) 2–3] vs. 3 days [IQR 2–4]; p 0.002). Although non-inferiority of early oral switch was found in the per-protocol population, the intervention was not non-inferior in the intent-to-treat population. [ABSTRACT FROM AUTHOR]

Early adverse parenting predicts various negative outcomes, including psychopathology and altered development. Animal work suggests that adverse parenting might change amygdala–prefrontal cortex (PFC) circuitry, but work in humans remains correlational. The present study leveraged data from a randomized controlled trial examining the efficacy of an early parenting intervention targeting parental nurturance and sensitivity (Attachment and Biobehavioral Catch-up [ABC]) to test whether early parenting quality causally affects amygdala-PFC connectivity later in life. Participants (N = 60, mean age = 10.0 years) included 41 high-risk children whose parents were referred by Child Protective Services and randomly assigned to receive either ABC (n = 21) or a control intervention (n = 20) during the children's infancy and a comparison sample of low-risk children (n = 19). Amygdala-PFC connectivity was assessed via functional magnetic resonance imaging while children viewed fearful and neutral faces. Across facial expressions, ABC produced different changes than the control intervention in amygdala-PFC connectivity in response to faces. The ABC group also exhibited greater responses than the control intervention group to faces in areas classically associated with emotion regulation, including the orbitofrontal cortex and right insula. Mediation analysis suggested that the effect of ABC on PFC activation was mediated by the intervention's effect on amygdala-PFC connectivity. Results provide preliminary causal evidence for the effect of early parenting intervention on amygdala-PFC connectivity and on PFC responses to face viewing. Findings also highlight amygdala-PFC connectivity as a potential mediator of the effects of early parenting intervention on children's emotion regulation development. Intervening Early With Neglected Children; https://clinicaltrials.gov/ ; NCT02093052. We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

The excess neonatal adiposity is considered a risk factor for the development of childhood obesity and the birth weight is a marker of health throughout life. To evaluate the effect of a lifestyle intervention conducted among pregnant women with overweight on neonatal adiposity and birth weight. A total of 350 pregnant women were recruited and randomly allocated into the control (CG) and intervention (IG) groups. Pregnant women in the IG were invited to participate in three nutritional counselling sessions based on encouraging the consumption of unprocessed and minimally processed foods, rather than ultra-processed foods, following the NOVA food classification system, which categorizes foods according to the extent and purpose of industrial processing, and the regular practice of physical activity. Neonatal adiposity was estimated using a previously validated anthropometric model. Adjusted linear regression models were used to measure the effect. Adopting the modified intention-to-treat principle, data from 256 neonates were analyzed for birth weight, and data from 163 for body composition estimation. The treatment had no effect on the proportion of fat mass [β 0.52 (95 % CI −1.03, 2.06); p =.51], fat-free mass [β −0.50 (95 % CI −2.45, 1.45); p =.61] or birth weight [β 53.23 (95 % CI −87.19, 193.64); p =.46]. In the present study, the lifestyle counselling used had no effect on neonatal adiposity or birth weight. Future studies should investigate the effect of more intensive interventions. • The intervention based on NOVA did not cause an undesirable effect on foetal development. • The nutritional intervention based on NOVA did not impair neonatal anthropometry. • Future research is needed to elucidate whether maternal lifestyle intervention can influence neonatal body composition. [ABSTRACT FROM AUTHOR]

This analysis of secondary outcomes investigated the applicability of supramaximal high-intensity interval training (HIT) with individually prescribed external intensity performed on stationary bicycles. Sixty-eight participants with a median (min; max) age of 69 (66; 79), at the time not engaged in regular exercise were randomized to 25 twice-weekly sessions of supramaximal HIT (20-min session with 10 × 6-s intervals) or moderate-intensity training (MIT, 40-min session with 3 × 8-min intervals). The primary aim was outcomes on applicability regarding; adherence to prescribed external interval intensity, participant reported positive and negative events, ratings of perceived exertion (RPE 6–20), and affective state (Feeling Scale, FS -5–5). A secondary aim was to investigate change in exercise-related self-efficacy (Exercise Self-Efficacy Scale) and motivation (Behavioural Regulations in Exercise Questionnaire-2). Total adherence to the prescribed external interval intensity was [median (min; max)] 89 % (56; 100 %) in supramaximal HIT, and 100 % (95; 100 %) in MIT. The supramaximal HIT group reported 60 % of the positive (112 of 186) and 36 % of the negative (52 of 146) events. At the end of the training period, the median (min; max) session RPE was 15 (12; 17) for supramaximal HIT and 14 (9; 15) for MIT. As for FS, the median last within-session rating was 3 (−1; 5) for supramaximal HIT and 3 (1; 5) for MIT. Exercise-related motivation increased (mean difference in Relative Autonomy Index score = 1.54, 95 % CI [0.69; 2.40]), while self-efficacy did not change (mean difference = 0.55, 95 % CI [-0.75; 1.82]), regardless of group. This study provide support for supramaximal HIT in supervised group settings for older adults. • Supramaximal HIT was well-tolerated by non-exercising older adults. • Supramaximal HIT participants reported more positive than negative events. • The findings provide support for the applicability of supramaximal HIT. [ABSTRACT FROM AUTHOR]

Experimental studies suggested that vitamin K supplementation may retard arterial calcification. Recently, serum calcification propensity time (T 50) has been suggested as a functional biomarker for arterial wall calcification propensity. In this post-hoc analysis of a clinical trial, we evaluated the effect of six-month oral vitamin K supplementation on T 50 and assessed the correlation between T 50 and imaging arterial calcification parameters in people with type 2 diabetes (T2DM). This double-blind, randomized, placebo-controlled trial included 68 participants (age = 69 ± 8 years, 76% male) with T2DM. Participants were assigned to menaquinone-7 (360 μg/day; n = 35) or placebo (n = 33). T 50 was measured via nephelometry in serum collected at baseline, three and six months. Arterial calcification was measured at baseline and six months via 18F–Na PET-CT and conventional CT using Target-to-Background ratio (TBR) and Agatston score. Longitudinal analysis of covariance adjusted for baseline T 50 was used to study the treatment effect. Spearman's correlation was used to assess the correlation between T 50 and imaging calcification parameters. Median baseline T 50 was similar in the vitamin K (350 [321–394] minutes) and placebo groups (363 [320–398]). There was no significant difference in T 50 between treatment arms over time (ẞ = 1.00, 95%C.I. = 0.94–1.07, p = 0.982). The correlation coefficient of T 50 with TBR and Agatston score at baseline were −0.185 (p = 0.156) and −0.121 (p = 0.358), respectively. No effect of vitamin K supplementation on T 50 was observed in T2DM. Moreover, T 50 did not correlate with TBR and Agatston score. Further research on vitamin K in arterial calcification and on the validity of T 50 as arterial calcification marker is warranted. [Display omitted] • Vitamin K did not improve serum calcification propensity time in type 2 diabetes. • Serum calcium propensity time did not correlate with PET-CT and CT parameters. • Further research on the role of vitamin K in arterial calcification is warranted. • New research on the validity of T 50 as measure of arterial calcification is needed. [ABSTRACT FROM AUTHOR]

Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease characterized by increasingly worsening ataxia and non-ataxia features, negatively impacting patients' quality of life. This study was designed to test formally evaluate whether oral trehalose was effective in SCA3 patients. In this double-blind, randomized controlled trial, SCA3 patients received either 100 g oral trehalose or 30 g maltose to improve ataxia severity over six months. We also measured other clinical (non-ataxia), patient-reported (quality of life, motivations), and safety endpoints. An unscheduled interim analysis was conducted using two-way ANOVAs to analyze the interaction between time (baseline, 3-months, 6-months) and intervention (Trehalose vs. Placebo). Fifteen participants (Trehalose = 7 vs. Placebo = 8) completed the study at the time of interim analysis. There was no interaction effect on the ataxia severity, and available data suggested an estimated sample size of 132 (66 per arm) SCA3 patients required to demonstrate changes in a 6-month trial. There were significant interaction effects for executive function (ƞ2 = 0.28–0.43). Safety data indicated that 100 g oral trehalose was well-tolerated. We performed an unplanned interim analysis due to a slow recruitment rate. The new estimated sample size was deemed unfeasible, leading to premature termination of the clinical trial. In this small, current sample of SCA3 patients, 100 g oral trehalose did not differentially impact on ataxia severity compared to placebo. Interestingly, our findings may suggest an improvement in executive function. Future efforts will require a large multi-country, multi-center study to investigate the potential effect of trehalose. • A positive open label pilot study led to a RCT of oral trehalose in SCA3. • Unexpectedly slow recruitment rate led to an unplanned interim analysis. • Unrealistic sample size recalculation warranted premature termination. • Oral trehalose did not improve SARA scores or quality of life in SCA3. • 100 g oral trehalose and 30 g maltose (placebo) were well-tolerated. [ABSTRACT FROM AUTHOR]

• Home-visiting interventions have positive effects on child cognitive development, parenting beliefs and parenting practices of caregivers in rural China. • Home-visiting interventions have null effects on child social-emotional development in rural China. • Three mechanisms are identified through which interventions are able to raise child cognitive development. • Shifting parenting beliefs; increasing parenting practices; and shifting parenting beliefs thus fostering better parenting practices of primary caregivers are the three mechanisms that are driving our overall results of the impact of home-visiting interventions on early child development. To better understand the impacts of parenting interventions (e.g., parental training of psychosocial stimulating activities) on child developmental outcomes and design effective policies to benefit young children, it is essential to identify the mechanisms through which the interventions work. To this end, this paper presents the results of two randomized controlled trials that offered home visitation, parenting trainings to 435 households (with 527 households as the control group) in 174 villages across three provinces in China. The findings from the randomized controlled trials showed that the interventions significantly improved child cognitive development and had a positive effect on the primary caregivers' parenting practices and their parenting beliefs. The analysis suggests three possible mechanisms through which the parenting interventions affected child cognitive development: changing the parenting beliefs of the primary caregivers, shifting the parenting practices of the primary caregivers, and improving the primary caregivers' parenting beliefs, thus fostering better parenting practices. [ABSTRACT FROM AUTHOR]

Despite their proliferation, limited knowledge exists regarding possible benefits of brief mindfulness ecological momentary interventions (MEMIs) for social anxiety disorder (SAD). Propositions that MEMIs could alleviate SAD symptoms and related clinical outcomes remain untested. This trial evaluated a 14-day MEMI for SAD. Participants with self-reported SAD were randomized to MEMI (n = 96) or self-monitoring app (SM; n = 95). Whereas MEMI instructed mindfulness exercises, SM prompted only self-monitoring five times daily for 14 days. Participants completed state-level self-reports of depression, anxiety, and mindfulness pre-post-mindfulness practice and SAD symptoms, worry, depression severity, repetitive negative thinking, and trait mindfulness at pre-randomization, post-intervention, and 1-month follow-up (1MFU). Hierarchical linear modeling was conducted. The MEMI yielded statistically significantly larger improvements in momentary depression, anxiety, and mindfulness (Cohen's d = −0.10–0.11). Although no between-group effects emerged in alleviating SAD fear and avoidance, excessive worry, depression severity, repetitive negative thinking, and trait mindfulness (−0.13–0.15), within-group effects were significantly small-to-large from pre-post and pre-1MFU (−4.62–0.67). A significant reduction in depression severity occurred in MEMI (−0.63–−0.60) but not SM (−0.31–−0.29). Brief MEMI and SM yielded nondifferent sustained effects on SAD, comorbid symptoms, and risk factors, highlighting its potential value within stepped-care delivery settings. • MEMI (vs. SM) notably improved state depression, anxiety, and mindfulness. • MEMI and SM enhanced SAD, worry, repetitive thinking, and trait mindfulness. • Depression severity was reduced in the MEMI but not the SM arm. • Brief MEMI might be efficacious for targeting pathological worry but not SAD. • MEMIs for SAD must be high-intensity and have exposure therapy to be efficacious. [ABSTRACT FROM AUTHOR]

Evaluate and compare the efficacy and safety of molnupiravir and favipiravir in outpatients with mild to moderate COVID-19 and at risk of severe COVID-19. In an open-label, parallel-group, multicenter trial in Thailand, participants with moderate COVID-19 and at least one factor associated with severe COVID-19 were randomly assigned 1:1 to receive oral molnupiravir or oral favipiravir (standard of care). Phone calls for remote symptom assessment were made on Days 6, 15, and 29. Participants with worsening symptoms were instructed to return to the hospital. The primary endpoint was pulmonary involvement by Day 29, as evidenced by ≥2 of the following: dyspnea, oxygen saturation <92% or imaging. Nine hundred seventy-seven participants (487 molnupiravir, 490 favipiravir) were enrolled from 8 July 2022 to 19 January 2023. 98% had received ≥1 dose of COVID-19 vaccine and 83% ≥3 doses. By Day 29, pulmonary involvement occurred in 0% (0/483) in molnupiravir arm versus 1% (5/482) in favipiravir arm (−1.0%; Newcombe 95.2% CI: −2.4% to −0.0%; P = 0.021); all-cause death in 0% (0/483) and <1% (1/482); COVID-19 related hospitalization in <1% (1/483) and 1% (3/482); treatment-related adverse event in 1% (5/483) and 1% (4/486); and serious adverse event in 1% (4/483) and 1% (4/486). Favipiravir and molnupiravir had a similar efficacy and safety profile. Whether either of the two reduced the risk of complications during the omicron era in this population with a low risk of pulmonary involvement and a high vaccine coverage remains unclear. There were no differences in any of the safety endpoints. TCTR20230111009. [ABSTRACT FROM AUTHOR]

Leveraging military veterans' intimate relationships during treatment has the potential to concurrently improve posttraumatic stress disorder (PTSD) symptoms and relationship quality. Cognitive-Behavioral Conjoint Therapy (CBCT) and an 8-session Brief Cognitive-Behavioral Conjoint Therapy (bCBCT) are manualized treatments designed to simultaneously improve PTSD and relationship functioning for couples in which one partner has PTSD. Although efficacious in improving PTSD, the effects of CBCT on relationship satisfaction are small, especially among veterans. Intranasal oxytocin, which targets mechanisms of PTSD and relationship quality, may enhance the efficacy of bCBCT. The purpose of this 4-year clinical trial is to compare the outcomes of bCBCT augmented with intranasal oxytocin versus bCBCT plus placebo. We will also explore potential mechanisms of action: self-reported communication skills, empathy, and trust. We will recruit 120 dyads (i.e., veteran with PTSD and their intimate partner) from the VA San Diego Healthcare System. Veterans will be administered 40 international units of oxytocin (n = 60) or placebo (n = 60) 30 min before each of 8 bCBCT sessions delivered via telehealth. Clinical and functioning outcomes will be assessed at five timepoints (baseline, mid-treatment, post-treatment, and 3- and 6-month follow-up). Study findings will reveal the efficacy of oxytocin-assisted brief couple therapy for PTSD, which could serve as highly scalable option for couples coping with PTSD, as well as provide preliminary evidence of interpersonal mechanisms of change. ClinicalTrials.gov Identifier: NCT06194851 [ABSTRACT FROM AUTHOR]

Individuals with a history of moderate-severe traumatic brain injury (TBI) experience a significantly higher prevalence of insomnia compared to the general population. While individuals living with TBI have been shown to benefit from traditional insomnia interventions (e.g., face-to-face [F2F]), such as Cognitive Behavioral Therapy for Insomnia (CBT I), many barriers exist that limit access to F2F evidence-based treatments. Although computerized CBT-I (CCBT-I) is efficacious in terms of reducing insomnia symptoms, individuals with moderate-severe TBI may require support to engage in such treatment. Here we describe the rationale, design, and methods of a randomized controlled trial (RCT) assessing the efficacy of a guided CCBT-I program for reducing insomnia symptoms for participants with a history of moderate-severe TBI. This is an RCT of a guided CCBT-I intervention for individuals with a history of moderate-severe TBI and insomnia. The primary outcome is self-reported insomnia severity, pre- to post-intervention. Exploratory outcomes include changes in sleep misperception following CCBT-I and describing the nature of guidance needed by the Study Clinician during the intervention. This study represents an innovative approach to facilitating broader engagement with an evidence-based online treatment for insomnia among those with a history of moderate-severe TBI. Findings will provide evidence for the level and nature of support needed to implement guided CCBT-I. Should findings be positive, this study would provide support for a strategy by which to deliver guided CCBT-I to individuals with a history of moderate-severe TBI. • There is a high prevalence of sleep disorders, including insomnia, following moderate-severe traumatic brain injury (TBI). • Computerized Cognitive Behavioral Therapy for Insomnia (CCBT-I) may help address barriers to accessing traditional treatments for insomnia. • Individuals with moderate-severe TBI often have impairments that may interfere with the uptake of CCBT-I. • Provider supported CCBT-I may increase efficacy of CCBT-I among some cohorts, such as those with a history of moderate-severe TBI. • This is a randomized controlled trial of a CCBT-I intervention for individuals with current insomnia and a history of moderate-severe TBI. • Positive results could support the development of a stepped-care model of CCBT-I following moderate-severe TBI. [ABSTRACT FROM AUTHOR]

Multisystem functional somatic disorder is characterized by specific patterns of persistent physical symptoms with a complex biopsychosocial etiology. The disorder can lead to disability and personal suffering. Current treatment options require specialized settings, therefore patients often wait a long time to receive specific treatment. Patient education is considered important in most treatment programs, but has only been investigated sparsely as a stand-alone treatment. Pharmacological treatment is limited to tricyclic antidepressants in low doses with no antidepressant properties. Duloxetine has been found effective in single organ functional disorders. As a treatment for multisystem functional somatic disorder, duloxetine could reduce symptoms and treat comorbid anxiety and depression. It may furthermore enhance the effect of patient education through a hypothesized effect on cognitive functioning. The purpose of the EDULOX trial is to study psycho-EDUcation and duLOXetine alone and in combination. This is a nested study design. The parent trial "EDULOX1" (n = 424) will compare a patient education program with enhanced usual care in an open-labelled, randomized controlled trial. In addition to this, eligible participants will furthermore receive either duloxetine or active placebo in the nested, double-blinded, randomized controlled trial, "EDULOX2" (n = 212). Patient and clinician reported outcomes will be collected through questionnaires. The EDULOX trial may establish evidence for treatments applicable for the majority of patients with multisystem functional somatic disorder. If effective, duloxetine would be a more tolerable pharmacological treatment option that can target comorbid depression and anxiety, and potentially boost the effect of patient education. Trial registration number The study is registered at www.clinicaltrials.gov (NCT06232473) and the internal list of research projects at the Region of Central Denmark (Case number 1-16-02-305-23). Approval from the Danish Medical Research Ethics Committees (Case number: 2212291) and the Danish Medicines Agency was obtained under EudraCT Number: 2022-002780-30 and Sponsor's Protocol Code Number: 9515. [ABSTRACT FROM AUTHOR]

Midlife hypertension is associated with cognitive decline and Alzheimer's disease and related dementia (ADRD), suggesting that blood pressure control may be a therapeutic target for dementia prevention. Given excess hypertension in non-Hispanic Black (NHB) adults, blood pressure control may also reduce ADRD disparities. We describe a pilot randomized controlled trial (RCT) to evaluate the feasibility and preliminary efficacy of a multicomponent lifestyle-based intervention versus enhanced usual care on cognition among middle-aged NHB adults. The Food Resources and Kitchen Skills plus Aerobic Training (FoRKS+) study is a 2-arm, single-blinded trial that compares those receiving the FoRKS+ program (target N = 64) versus those receiving enhanced usual care (target N = 64) in local federally-qualified health centers. Key eligibility criteria include self-identified NHB adults between ages 35–75 with a mean systolic blood pressure ≥ 130 mm/Hg obtained from 24-h ambulatory blood pressure monitoring. The FoRKS+ program includes 5 weeks of hypertension self-management courses, 11 weeks of nutrition courses, and 12 weeks of aerobic training in dietitian and health coach-led virtual groups. We will collect data on primary cognitive outcomes, feasibility, hypothesized intervention mediators and moderators, and demographic and health covariates at baseline, near intervention weeks 16-, and 28 (primary outcome assessment), and week 52 follow-up. We will use mixed-effects modeling to examine intervention effects on cognition. This pilot RCT will examine the feasibility and preliminary effects of a multicomponent lifestyle intervention on cognitive function in NHB adults, which may have implications for reducing health disparities in ADRD. [ABSTRACT FROM AUTHOR]

Chinese herbal medicine is increasingly used as complementary therapy to manage nausea and vomiting in different cultures. One such herbal recipe is the Hezhong granules, which contain classical antiemetic formulations, and are commonly used to prevent chemotherapy-induced nausea and vomiting (CINV). Modern pharmacological studies have shown that the key components of Hezhong granules, including Pinellia ternata (Thunb.), Evodia rutaecarpa (Juss.), and Zingiber officinale exhibit significant antiemetic and antitumor properties. Despite this promising evidence, controlling CINV remains a significant challenge in cancer treatment. Moreover, there is a lack of scientifically designed clinical trials to validate the efficacy and safety of classical antiemetic formulas for CINV interventions. To investigate the efficacy and safety of Hezhong granules in preventing CINV in patients with advanced colorectal cancer (CRC). This study was conducted between October 2020 and February 2022 in 12 hospital wards in Southwest China. In this multicenter, randomized controlled trial, we enrolled patients with advanced CRC who received fluorouracil-based chemotherapy. The patients were randomly assigned in a 1:1 ratio to either the Hezhong granule group (receiving a 5-HT3-receptor antagonist, dexamethasone, and Hezhong granules) or the placebo group (receiving a 5-HT3-receptor antagonist, dexamethasone, and placebo) during the first and second courses of chemotherapy. A 5-day diary was provided to all patients. Acute and delayed CINV were defined as CINV occurring within 24 h or between 24 and 120 h after the start of treatment. The primary endpoints were complete response rate (CRR, defined as the proportion of patients without nausea/vomiting) and objective response rate (ORR, defined as the proportion of patients without nausea/vomiting plus mild nausea/vomiting) for both acute and delayed CINV. Secondary endpoints were the daily rates of CINV events and Functional Living Index-Emesis (FLIE). To identify the predictors of CINV, we conducted multivariate ordered logistic regression analysis. This study was registered with the Chinese Clinical Trial, number ChiCTR2100041643. A total of 120 participants were randomly assigned, of whom 112 (56/56) completed two cycles and were included in the full analysis. In the acute phase, there were minor improvements in the Hezhong granule group, but there were no significant differences in the CRRs for nausea and vomiting (mean difference:10.7 %, P = 0.318, 0.324), while the ORRs increased by approximately 17.5 % (mean difference:16.1 %, P = 0.051; 17.9 %, P = 0.037, respectively). In the delayed phase, significant improvements of approximately 20 % were observed in both the CRRs (mean difference:19.6 %, P = 0.053; 21.4 %, P = 0.035) and ORRs (mean difference:17.9 %, P = 0.037, 0.043) for nausea and vomiting. Additionally, the daily rate of CINV events showed a mean difference of 19 % (P < 0.05). According to FLIE scores, approximately 70 % of patients who received Hezhong granules reported an improvement in their quality of life, with CINV symptoms having"no impact on daily life (NIDL)". No serious adverse events were attributed to herbal medicine. Hezhong granules proved to be both effective and well-tolerated in preventing CINV in patients with advanced CRC, with notable benefits in preventing delayed CINV. These promising results set the stage for subsequent phase III clinical trials and experimental research on Hezhong Granules. [Display omitted] • Hezhong granule can increase the complete response rate of CINV by about 10 %–20 %. • Hezhong granule can increase the objective response rate of CINV by about 16 %–18 %. • Hezhong granule show better efficacy in preventing delayed CINV. • Hezhong granule is well tolerated and can significantly improve the quality of life of patients. [ABSTRACT FROM AUTHOR]

People engaged in treatment for opioid use disorder (OUD) report struggling with whether and how to disclose, or share information about their OUD history and/or treatment with others. Yet, disclosure can act as a gateway to re-establishing social connection and support during recovery. The current study describes a pilot randomized controlled trial of Disclosing Recovery: A Decision Aid and Toolkit, a patient decision aid designed to facilitate disclosure decisions and build disclosure skills. Participants (n = 50) were recruited from a community-based behavioral health organization in 2021–2022 and randomized to receive the Disclosing Recovery intervention versus an attention-control comparator. They responded to surveys immediately after receiving the intervention as well as one month following the intervention at a follow-up appointment. Primary outcome analyses examined indicators of implementation of the intervention to inform a future efficacy trial. Secondary outcome analyses explored impacts of the intervention on the decision-making process, disclosure rates, and relationships. Participants were successfully recruited, randomized, and retained, increasing confidence in the feasibility of future efficacy trials to test the Disclosing Recovery intervention. Moreover, participants in the Disclosing Recovery intervention agreed that the intervention is acceptable, feasible, and appropriate. They additionally reported a higher quality of their decision-making process and decisions than participants in the comparator condition. At their follow-up appointment, participants with illicit opioid use who received the Disclosing Recovery intervention were less likely to disclose than those who received the comparator condition. Moreover, significant interactions between illicit opioid use and the intervention condition indicated that participants without illicit opioid use who received the Disclosing Recovery intervention reported greater closeness to and social support from their planned disclosure recipient than those who received the comparator condition. The Disclosing Recovery intervention appears to be an acceptable, feasible, and appropriate patient decision aid for addressing disclosure processes among people in treatment for OUD. Moreover, preliminary results suggest that it shows promise in improving relationship closeness and social support in patients without illicit opioid use. More testing is merited to determine the intervention's efficacy and effectiveness in improving relationship and treatment outcomes for people in treatment for OUD. • People in opioid use disorder (OUD) treatment struggle with disclosure decisions. • Disclosing Recovery is a patient decision aid for disclosure decisions and skills. • It appears to be acceptable, appropriate, and feasible. • Future trials should examine its impacts on relationship and treatment outcomes. [ABSTRACT FROM AUTHOR]

To compare the efficacy and safety of basal-plus (BP) insulin regimen with or without sitagliptin in non-critically ill patients with type 2 diabetes (T2D). This open-label, randomized clinical trial included inpatients with a previous diagnosis of T2D and blood glucose (BG) between 180 and 400 mg/dL. Participants received basal and correctional insulin doses (BP regimen) either with or without sitagliptin. The primary outcome was the difference in the mean daily BG among the groups. Seventy-six patients (mean age 60 years, 64 % men) were randomized. Compared with BP insulin therapy alone, the sitagliptin-BP combination led to a lower mean daily BG (158.8 vs 175.0 mg/dL, P = 0.014), a higher percentage of readings within a BG range of 70–180 mg/dL (75.9 % vs 64.7 %, P < 0.001), and a lower number of BG readings >180 mg/dL (P < 0.001). Sitagliptin-BP resulted in fewer basal and supplementary insulin doses (P = 0.024 and P = 0.017, respectively) and lower daily insulin injections (P = 0.023) than those with insulin alone. The proportion of patients with hypoglycemia was similar in the two groups. For inpatients with T2D and hyperglycemia, the sitagliptin and BP regimen combination is safe and more effective than insulin therapy alone. Clinicaltrials.gov identifier: NCT05579119 [Display omitted] • Previous studies have found that basal and correctional insulin doses (basal-plus regimen) with sitagliptin are similar to the basal-bolus insulin regimen in managing hyperglycemia in a hospital setting. However, whether this combination is better than basal-plus regimen alone is unclear. • Our research showed that combining sitagliptin with a basal-plus insulin regimen leads to lower daily blood glucose levels, a comparable risk of hypoglycemia, and lower insulin doses than the basal-plus regimen alone. • These results are significant because using DPP-4 inhibitors with basal-plus insulin therapy simplifies hospital diabetes management for healthcare professionals, improves treatment adherence, and, by extension, leads to better patient outcomes. [ABSTRACT FROM AUTHOR]

Rural populations experience a higher prevalence of both food insecurity and type 2 diabetes mellitus (T2DM) than metropolitan populations and face many challenges in accessing resources essential to optimal T2DM self-management. This study aims to address these challenges by delivering a T2DM-appropriate food box and recipes directly to rural participants' homes. This is a comparative effectiveness randomized controlled trial including 400 English- or Spanish-speaking rural adult participants with T2DM (HbA1c ≥6.5%) experiencing food insecurity. Participants are randomly assigned to a 3-month Healthy Food Delivery Intervention (HFDI) plus one 60-min virtual consultation with a diabetes educator or consultation only. The HFDI includes a weekly food box delivery with recipes. Data are collected at pre-intervention, 3-months (post-intervention), 9-months, and 15-months. The primary outcome is change in HbA1c, with secondary measures including diet quality (Healthy Eating Index-2015, calculated from one 24-h dietary recall at each data collection time point), cardio-metabolic risk factors (i.e., blood pressure, lipids, body mass index, glucose), and patient-centered outcomes (e.g., T2DM self-efficacy, T2DM-related distress). Process evaluation data (e.g., successful food box deliveries, diabetes educator consultation attendance, intervention satisfaction) are collected during and post-intervention (3-months). A cost-effectiveness analysis based on traditional cost per quality-adjusted life year gain thresholds will be conducted to estimate the incremental cost-effectiveness between HFDI plus consultation and consultation alone. Findings from this study will provide evidence regarding the effectiveness of an intervention that promotes participant adherence and improves access to healthy food. Clinical Trial Registration: NCT04876053 [ABSTRACT FROM AUTHOR]

Randomized controlled trials include interim monitoring guidelines to stop early for safety, efficacy, or futility. Futility monitoring facilitates re-allocation of limited resources. However, conventional methods for interim futility monitoring require a trial to accrue nearly half of the outcome data to make a reliable early stopping decision, limiting its benefit. As early stopping for futility will not inflate type-I error, these analyses are an appealing venue for incorporating external data to improve efficiency. We propose a Bayesian approach to futility monitoring leveraging real world data using Semi-Supervised MIXture Multi-source Exchangeability Models, which accounts for both measured and unmeasured differences between data sources. We implement futility monitoring using predictive probabilities and investigate the optimal timing with respect to the expected sample size under the null hypothesis. Because we only incorporate external data during the interim futility analysis the proposed design is not limited by type-I error inflation. When the external and trial data are exchangeable, the proposed method provides a roughly 70 person reduction in expected sample size under the null. Under scenarios where exchangeability does not hold, our approach still provides a 10–20 person reduction in expected sample size under the null with about 80% power. External data borrowing in interim futility monitoring is a promising venue to improve trial efficiency without type-I error inflation. Approaches that are acceptable to regulatory authorities and leverage the complementary strengths of real world and trial data are vital to more efficiently allocate limited resources amongst clinical trials. [ABSTRACT FROM AUTHOR]

This preregistered randomized controlled study investigated the effects of Video-Feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) on parents' secure base script knowledge (SBSK). Furthermore, we examined whether effects of VIPP-SD on sensitive caregiving and sensitive discipline behavior and parents' attitudes toward these behaviors were moderated by SBSK at baseline. Families (n = 445) with pre- and school-aged children (n = 890) were randomized to receive VIPP-SD or telephone calls. Results showed no effects of VIPP-SD on SBSK. Furthermore, there was no moderation of effects on sensitive caregiving or sensitive discipline behavior by SBSK. VIPP-SD promoted positive attitudes toward sensitive caregiving and sensitive discipline behavior. The latter effect was moderated by SBSK: parents with lower SBSK showed the strongest improvements in positive attitudes toward sensitive discipline behavior. This effect was driven by a subgroup of younger children. These findings highlight the potential importance of tailoring interventions to meet the specific needs of parents with varying levels of SBSK. • We found no effects of VIPP-SD on parental secure base script knowledge (SBSK). • SBSK moderates effects of VIPP-SD on discipline attitudes. • Parents with lower SBSK benefit most from VIPP-SD. • VIPP-SD is effective in promoting positive attitudes toward sensitivity. • Effects on promoting positive attitudes toward sensitivity are independent of SBSK. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the clinical efficacy and safety of administering intermittent theta burst stimulation (iTBS) to the medial prefrontal cortex for tobacco use disorder. A randomized sham-controlled trial was conducted, with 38 participants receiving 28 sessions of active (n=25) or sham (n=13) iTBS (2 sessions/day, 600 pulses/session, 110% resting motor threshold, AFz target) along with smoking cessation education (Forever Free © booklets) over 14 visits. Primary outcomes included self-reported cigarette consumption and abstinence, verified by urinary cotinine tests. Secondary outcomes included symptoms of tobacco use disorder, negative mood, and safety/tolerability. Both active and sham groups reported reduced cigarette consumption (β = −0.12, p = 0.015), cigarette craving (β = −0.16, p = 0.002), and tobacco withdrawal symptoms (β = −0.05, p < 0.001). However, there were no significant time x group interaction effects for any measure. Similarly, the two groups had no significant differences in urinary cotinine-verified abstinence. Adverse events occurred with similar frequency in both groups. There were no differences in cigarette consumption between the active and sham iTBS groups, both groups decreased cigarette consumption similarly. Further research is needed to compare iTBS to standard high-frequency rTMS and explore the potential differences in efficacy. Despite limitations, this study contributes to experimental design considerations for TMS as a novel intervention for tobacco and other substance use disorders, emphasizing the need for a more comprehensive understanding of the stimulation parameters and target sites. • Intermittent theta burst stimulation (iTBS) was tested for tobacco use disorder. • iTBS was administered on the medial prefrontal cortex for 14 visits. • Both active and sham iTBS reduced the number of cigarettes per day. [ABSTRACT FROM AUTHOR]

High prevalence and harmful consequences of hazardous drinking among medical-surgical patients underscore the importance of intervening with drinking to improve patients' health. This study evaluated a novel intervention, "Drinking Options - Motivate, Shared Decisions, Telemonitor" (DO-MoST). In a randomized design, 155 medical-surgical patients with untreated hazardous drinking were assigned to enhanced usual care or DO-MoST, and followed 3, 6, and 12 months later. We conducted intent-to-treat and per-protocol analyses. For the primary outcome, percent days of alcohol abstinence in the past 30 days, intent-to-treat analyses did not find superior effectiveness of DO-MoST. However, per-protocol analyses found abstinence increased between 3 and 12 months among participants assigned to DO-MoST who engaged with the intervention (n=46). Among DO-MoST-assigned participants who did not engage (n=27), abstinence stayed stable during follow-up. Group comparisons showed an advantage on abstinence for Engaged compared to Non-Engaged participants on change over time. Intent-to-treat analyses found that DO-MoST was superior to usual care on the secondary outcome of physical health at 12 months; per-protocol analyses found that Engaged DO-MoST-assignees had better physical health at 12 months than Non-Engaged DO-MoST-assignees. DO-MoST-assignees had lower odds of receiving substance use care during follow-up than usual care-assignees. Patients engaged in DO-MoST showed a greater degree of abstinence and better physical health relative to the non-engaged or usual care group. DO-MoST may be a source of alcohol help in itself rather than only a linkage intervention. Work is needed to increase DO-MoST engagement among medical-surgical patients with untreated hazardous drinking. • Untreated hazardous drinking harms medical-surgical patients and needs intervention. • RCT studied Drinking Options - Motivate, Shared Decisions, Telemonitor (DO-MoST). • Patients engaged in DO-MoST had better abstinence and physical health than others. • DO-MoST may be a source of alcohol help in itself, not only a linkage intervention. [ABSTRACT FROM AUTHOR]

• A randomized controlled trial to examine the effects of a nutrition education and a precise information (awareness-raising) intervention on dietary quality. • A significant and positive association between intervention and dietary quality is found. • The intervention effects are stronger for households with more than 25% and 50% of overweight people. Nutrition education interventions are widely used globally but with mixed results. We conducted a randomized controlled trial to examine the effects of a nutrition education and a precise message (awareness-raising) intervention on nutrition knowledge and dietary quality of households in rural China. Treatment groups first received a lecture on the Chinese Food Guide Pagoda, and then all family members were measured for height and weight and informed of household overweight status. We analyzed 358 households before and after this intervention. Participants in the treatment group increased their dietary knowledge by 6% and improved their dietary quality by 8% after the intervention. The intervention effects were stronger for households with more than 25% and 50% of overweight people. Our study provides evidence that an intervention based on general nutrition information and delivery of a precise message to households can effectively improve dietary quality. Our findings inform the food policy debate on whether nutrition information interventions are effective. Furthermore, to the best of our knowledge, this is the first study to evaluate the effectiveness of a nutrition information intervention to improve dietary quality in rural China. [ABSTRACT FROM AUTHOR]

• Upper-extremity musculoskeletal disorders are a prevalent public health issue. • A short spa therapy intervention did not improve function more than self-management. • Adherence to home exercise was greater for self-management than spa therapy. • Self-management interventions may reduce disability and pain. Musculoskeletal disorders (MSDs) are common in the workplace and are a public health issue. Persistent pain despite conservative treatment or surgery may lead to poor long-term outcomes. To compare the effect of a combined 6-day program of exercise, self-management workshops and spa therapy with self-management on functional capacity in personal and professional daily life at 3 months in people with musculoskeletal disorders. We conducted a prospective, randomized controlled trial. Participants were employed (any type of work) and aged between 18 and 65 years, with latent or symptomatic upper extremity MSDs, with or without a history of sick leave. They were randomized to participate in 6 days (2 h per day) of spa therapy, exercise, and self-management workshops immediately (intervention) or at 3 months (control). The control group performed self-management until 3 months. The primary outcome was the score on the self-reported Quick Disability of Arm-Shoulder-Hand (QuickDASH) at 3 months. The primary analysis was conducted using analysis of covariance with baseline QuickDASH score as the covariate. In total, 150 participants were randomized (85 % women): 78 to the control group and 72 to the intervention group. At 3 months, the QuickDASH total and work scores did not differ between groups (effect-size [ES] = -0.15, 95 %CI, -0.38 to 0.09, p = 0.215, and ES = -0.11, 95 % CI, -0.35 to 0.12, p = 0.343). However, QuickDASH sport/performing arts score was significantly different between randomization groups at 3 months (ES =-0.25, 95 % CI, -0.48 to -0.02, p = 0.035). This study provided no evidence in favor of a short-course, personalized self-management, intensive spa therapy intervention over self-management alone for the management of upper-extremity MSDs. Trial registration: ClinicalTrials.gov (NCT02702466) retrospectively registered. [ABSTRACT FROM AUTHOR]

Most people with dementia live at home and depend on informal caregivers for care. Both caregivers and persons with dementia can experience negative psychological and behavioural effects as the disease progresses. Non-pharmacological interventions can alleviate these effects and dyadic interventions, involving both caregiver and person with dementia, may be particularly effective. In this systematic review, the effect of dyadic interventions involving community-dwelling persons with dementia and their informal caregivers was researched. This article is an update of a review of dyadic interventions up to 2012 (Van't Leven et al., 2013). Twenty-two randomized controlled trials published between January 2012 and March 2023 met eligibility criteria, representing 3857 dyads. Results of a meta-analysis showed no overall intervention effect. Thirteen studies reported positive intervention effects, 9 studies reported no intervention effects. Intervention content and participant characteristics and knowledge of the disease varied widely between the studies reviewed. Effective interventions were those that matched activities for the person with dementia to their interests and abilities and educating the caregiver about dementia and communication. Interventions of moderate length (3–4 months) tended to be more effective than longer or shorter interventions. Future studies should further explore the factors contributing to the effects of dyadic interventions. • Effective interventions adapt activities to preferences of the person with dementia. • Interventions most frequently improved quality of life and neuropsychiatric symptoms. • Interventions with a duration of 3–4 months were most effective. • Symptom severities and specific needs influence the efficacy of dyadic interventions. [ABSTRACT FROM AUTHOR]